Human immunodeficiency virus-infected (HIV[+]) women have a several-fold increased risk of invasive cervical cancer (ICC) as well as increased risk of cervical precancer. In low- and middle-income countries (LMICs), ICC is the 1st or 2nd most common cause of cancer and cancer-related death in women. Rates of ICC and ICC-related mortality are particularly high in Sub-Saharan Africa, which also has the highest rates of HIV infection in the world. Although prophylactic HPV vaccines may be the optimal cervical cancer prevention strategy, 2-3 generations of at-risk HIV[+] women are already highly exposed to human papillomavirus (HPV) and would not benefit from (and will not be immunized with) HPV vaccine. Thus cervical cancer screeing is needed for the foreseeable future. However, Pap testing is expensive and requires a complex clinical and lab infrastructure that does not generally exist in LMICs; strategies based on high-risk HPV (hrHPV) testing or visual inspection after acetic acid (VIA) are promising but are either too non-specific, leading to over-referral for colposcopy or over-treatment, or are too Insensitive, respectively. Thus, inexpensive, easily implemented, and effective cervical cancer screening methods are greatly needed in Sub-Saharan Africa, especially for HIV[+] women. We propose a cervical cancer screening study of ~7,200 HIV[+] women, aged 30-54 years, living in Rwanda, exploiting our existing research infrastructure. We will evaluate screening tests (hrHPV testing, VIA and Pap), traditional triage tests (HPV16/18/45 detection, VIA, Pap), and promising new biomarkers for triage (E6/E7, Ki-C67, TOP2a, CDKN2A, and genotype-specific HPV viral methylation and load) of screen-positive women. A random sample of all women and all screen positives will undergo rigorous disease ascertainment to obtain unbiased estimates of sensitivity, specificity, and positive and negative predictive value. We will conduct a detailed micro-costing exercise that will inform our cost-effectiveness analysis of the different screening and management strategies. This will be the largest, most comprehensive study of cervical cancer screening in HIV[+] women living in Sub-Saharan Africa or anywhere.